Blood vessels are a tissue central to many disease states. One such disease state is drug induced vascular injury (DIVI), a pathological insult to blood vessels that occurs after the administration of a drug. DIVI causes smooth muscle cell (SMC) death and hemorrhage and is characterized by the extravasation of red blood cells (RBCs) from the vascular lumen into surrounding SMC layers. This phenomenon occurs without overt damage to the endothelial cells (ECs). The cause of DIVI is poorly understood but its occurrence often halts in vivo testing of candidate drugs.
The predilection for DIVI is unclear. The central and only specific event in DIVI is the extravasation of RBCs into the media of the effected blood vessels. Currently, the molecular mechanisms of DIVI are unclear and no specific biomarkers are known that allow DIVI to be distinguished from other forms of vascular injury. It is contemplated that improved understanding of the mechanisms of DIVI will improve the screening of drugs under development and better correlate the significance of in vivo animal testing and human susceptibility to DIVI.
It would therefore be desirable to develop an in vitro model of a small diameter blood vessel to allow the study of a variety of vascular diseases and physiological mechanisms. In particular, the model would be used to investigate the mechanisms and biomarkers of DIVI in animals and humans. It would provide a platform for the screening of drugs under development and allow disease processes effecting small to medium sized vessels to be investigated.